In this mentored scientist development award for Dr. Xiangning Chen, sponsored by Dr. Kenneth Kendler, describes a 5-year, comprehensive training and research program for the genetics of nicotine, alcohol and other abused substances. Tobacco smoking, alcoholism and drug abuses are serious public health issues. Epidemiology studies have shown that genetics influences the behaviors of substance uses. However, the nature of these genetic factors remains largely unknown. The identification and characterization of these genetic factors would facilitate the prevention, diagnosis and treatment of substance abusers and/or dependents. In the program, four specific aims are proposed to facilitate professional growth and to cultivate independent research in the fields of substance abuse and behavioral genetics. The aims are: 1). To use bioinformatic tools and software to select, rank and prioritize candidate genes from linkage, microarray, pharmacology and animal model and behavioral studies;2).To use a case-control sample selected from the Virginia Twin Registry to identify genetic risk factors for nicotine dependence, alcohol dependence and other substance use disorders;3). To verify risk factors identified from aim 2 with a new case-control sample collected for alcohol dependence studies;and 4). To genotype those positive markers for the cotwins of subjects used in aim 2 and to use structural equation modeling and other statistical techniques to test if genetic risk factors identified in aims 2 and 3 are specific to each substance or shared between different substances. The training components focus on bioinformatics skills, statistical principles and methods, neural chemistry and pharmacology of abused substances and classification and diagnosis of substance abuse symptoms. The proposal integrates the training activities with the research plan to achieve the goal of independent research in the fields of drug abuse genetics.